This invention relates to apparatus for measuring the concentration of a substance in a liquid and particularly, but not exclusively, to apparatus for measuring the concentration of glucose in blood.
Devices for measuring blood glucose levels are invaluable for diabetics, especially devices that may be used by the sufferers themselves since they may then monitor their own glucose levels and take an appropriate dose of insulin. Correspondingly therefore the accuracy of such devices is very important since an inaccurate reading could lead to the wrong level of insulin being administered which could be very harmful.
It is also the case that in all practical blood glucose measuring systems at least part of the device, i.e. that part which comes into contact with the sample blood, is disposable. This means that it is particularly important that the cost particularly of any disposable parts can be minimised as a user will generally need large numbers of them regularly.
Known glucose measuring devices now favour an electrochemical measurement method over old colorimetric methods. The general principle is that an electric current is measured between two sensor parts called the working and reference sensor parts respectively. The working sensor part comprises an electrode onto which is laid a layer of enzyme reagent which comprises an enzyme and an electron mediator compound. When a potential is applied across the sensor parts a current is generated by the transfer of electrons from the substance being measured (the enzyme substrate), via the enzyme and to the surface of the electrode. The current generated is proportional to both the area of the sensor part and also the concentration of glucose in the test sample. Since the area of the working sensor part is supposedly known, the electric current should be proportional to the glucose concentration.
It has been recognised in the art that inaccurate results are obtained if the working sensor part is not fully covered with blood since then its effective area is reduced. Various ways of dealing with this problem have been proposed, two of which are disclosed in U.S. Pat. No. 5,628,890 and U.S. Pat. No. 5,582,697. Both of these methods rely on a unidirectional flow of blood across the surface of the test strip and both initiate the test measurement by detecting the presence of the sample liquid at an electrode or sensor part located downstream of the working sensor part.
The problem of insufficient sample liquid being present and thus the working sensor part not being completely covered may of course be reduced by reducing the size of the working sensor part. However a small area for the working sensor part tends to give a greater variability in calibrated results.
The present inventors have realised that as well as incomplete coverage of the working sensor part, inaccurate results can also arise from occasional defects in the production of the test strips for such devices and also from accidental damage to the working sensor part e.g by a user. As far as the inventors are aware, the only practical way to deal with this problem so far has been to ensure that the printing process used to produce the test strips is as accurate as possible and to rely on adequate quality control.
It is an object of the present invention at least partially to alleviate the above-mentioned disadvantages and when viewed from a first aspect the invention provides a method of measuring the concentration of a substance in a sample liquid comprising the steps of:
providing a measuring device having a first working sensor part, a second working sensor part and a reference sensor part;
applying the sample liquid to said measuring device;
measuring an electric current at each sensor part proportional to the concentration of said substance in the sample liquid;
comparing the electric current from each of the working sensor parts to establish a difference parameter; and
giving an indication of an error if said difference parameter is greater than a predetermined threshold.
Thus it will be seen that in accordance with the invention the substance-concentration-dependent current is effectively measured twice and the two measurements compared so that each can be used as a check for the other.
The invention is considered to be particularly beneficial in the context of electrochemical assays in which the substance whose concentration it is desired to check, e.g. glucose in blood, reacts with an element of on the working sensor parts, e.g. an enzyme reagent, to generate charge carriers and thereby give rise to the electric current proportional to the concentration of the substance in the liquid.
Furthermore the measuring device used in this method is novel and inventive in its own right and thus from a second aspect the present invention provides a device for measuring the concentration of a substance in a sample liquid, said device comprising:
a reference sensor part,
a first working sensor part for generating charge carriers in proportion to the concentration of said substance in the sample liquid; and
a second working sensor part also for generating charge carriers in proportion to the concentration of said substance in the sample liquid.
Thus it will be seen that in accordance with the invention the measuring device compares the current passed by two working sensor parts as a result of their generation of charge carriers and gives an error indication if the two currents are too dissimilarxe2x80x94i.e. the current at one sensor part differs too greatly from what would be expected from considering the current at the other. Not only can this method detect when one of the sensor parts has not been properly covered with sample liquid, but it can also detect if there is a manufacturing defect in either sensor part or if either has been damaged after manufacture, since even with complete coverage of the working sensor parts, an anomalous current will arise at the affected sensor part in such circumstances.
In accordance with the invention the only type of defect or damage which would not necessarily be recognised is one which affected both of the working sensor parts to the same degree. However, this is logically less likely than a defect affecting a single working sensor part and is thus an improvement over the prior art. In practice such a likelihood is considered to be negligible. In any event the invention is not limited to providing just two working sensor parts and the skilled person could therefore choose to provide three or more working sensor parts to further reduce the probability that they are all affected by an identical defect.
Looking at the invention another way, it provides an arrangement whereby for a given total area of working sensor part and thus a given minimum sample volume, detection of inadequate fill and of defects or damage to the working sensor part can be provided by separating the area of the working sensor part into two.
Some or all of the sensor parts may be provided as part of an integrated device. Preferably however at least the working sensor parts are provided on a removable test member. Thus when viewed from a further aspect the present invention provides a test member for measuring the concentration of a substance in a sample liquid comprising:
a base member; and
two working sensor parts provided on the base member, each working sensor part being arranged in use to generate charge carriers in proportion to the concentration of said substance in the sample liquid.
Preferably a reference sensor part is also provided on the base member.
It will be appreciated by those skilled in the art that effectively what has been provided is a measuring device which is self-testing for proper use, damage and certain manufacturing defects. This is particularly beneficial in the context of a device in which the sensor parts are provided on a separate test member since this may typically be a mass-manufactured test strip, e.g. for measuring blood glucose levels. Such strips would typically be used by a lay person who would not necessarily treat them with sufficient care to prevent damage.
Since in accordance with the invention a damaged or defective test strip will be recognised, allowing it to be rejected, the accuracy of the final result and thus potentially the safety of a user is no longer solely dependent upon high manufacturing precision and proper careful use. At least in the latter regard, the preferred embodiments of the invention provide an additional layer of safety compared to known arrangements. Although it is of course not desirable that a large number of tests is rejected, in many circumstances it is more important that inaccurate results are not given.
The two working sensor parts may be arranged as convenient within the device, or in accordance with the preferred embodiment, on the test member. The device or test member may be arranged to allow the sample liquid to flow freely over the working sensor parts. More preferably however the sample liquid is constrained to flow substantially unidirectionally across the working sensor parts.
It is particularly preferred that the two working sensor parts are arranged one downstream of the other. This makes it possible to ensure that one of the sensor parts will always be completely covered before the other begins to be covered, thus avoiding the possibility, however small, that insufficient sample liquid is applied to cover both sensor parts and furthermore that each sensor part is partially covered by the same amount. It will be appreciated however that if the above-mentioned small risk is deemed acceptable, arrangements in accordance with the invention allow a much greater flexibility in the placement of the sensor parts than in known devices whilst still providing protection against an inadequate volume of sample liquid being used or other incorrect product usage or damage. Most preferably both working sensor parts are downstream of the reference sensor part.
The currents generated by the two working sensor parts may not be directly comparable, e.g. because the sensor parts are dissimilar, in which case the measuring device is preferably arranged to apply appropriate weights to the measurements returned by one or both working sensor parts to normalise them. The difference parameter could then for example be the simple arithmetic difference between the normalised current values. Preferably however both sensor parts comprise the same working material and alternatively, but preferably additionally, both working sensor parts have the same area. Thus it is most preferred that the two working sensor parts are substantially identical. This enables the difference parameter easily to comprise a direct comparison between the respective currents at the sensor parts in order to determine whether a reliable measurement of the substance concentration can be made.
The threshold used to determine an inaccurate measurement may be chosen as appropriate. Typically a threshold will be chosen empirically as a suitable value will depend on the inherent variability in the manufacturing process, the desired precision of results, etc. To some extent there is a trade-off between the accuracy which may be obtained by setting the threshold low and the proportion of measurements which are disregarded as being too inaccurate. Thus the threshold might advantageously be set at a level for example where no significant harm would be done to a patient relying on the results to administer insulin.
The difference parameter may be an absolute valuexe2x80x94e.g. the difference in currents measured at each sensor part, but is preferably dimensionlessxe2x80x94e.g. a percentage of one or other of the measured currents.
Preferably the currents are measured after a predetermined time, although this is not necessarily essential.
The actual current value used to calculate the concentration of the substance may just be that from one of the working sensor parts, but is preferably a combination thereof, e.g. the sum or mean of the two. This gives the advantage that the maximum effective working area is utilised which further helps to increase the precision of the results obtained.
A particularly preferred embodiment of the invention is a device for measuring the concentration of glucose in blood, in which the two working sensor parts and the reference sensor part are provided on a disposable test strip.